Aflibercept to treat retinopathy of prematurity: need for more research.

Until recently, the standard care for retinopathy of prematurity (ROP) was destructive treatment of the peripheral avascular retina, most often using laser therapy. Now, intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have been included in recommendations for treatment-warranted ROP. The three anti-VEGF agents used to treat ROP are bevacizumab, ranibizumab, and aflibercept and clinical trials using, a variety of treatment strategies, have shown all three are efficacious and easy to administer. Intravitreal Bevacizumab is most used in the US, and ranibizumab has been approved for ROP use in Europe. In 2023, the FDA approved aflibercept for treatment of severe ROP. We summarize the clinical trial results and provide a side-by-side comparisons of the three drugs. Despite FDA approval of the use of aflibercept to treat ROP, there is a need for more research as the body of knowledge regarding this agent to treat ROP is limited.

Can a Risk Factor Based Approach Safely Reduce Screening for Retinopathy of Prematurity?

Objective. Current American retinopathy of prematurity (ROP) screening guidelines is imprecise for infants ≥ 30 weeks with birth weights between 1500 and 2000 g. Our objective was to evaluate a risk factor based approach for screening premature infants at low risk for severe ROP. Study Design. We performed a 13-year review from Intermountain Health Care (IHC) data. All neonates born at ≤32 weeks were reviewed to determine ROP screening and/or development of severe ROP. Severe ROP was defined by stage ≥ 3 or need for laser therapy. Regression analysis was used to identify significant risk factors for severe ROP. Results. We identified 4607 neonates ≤ 32 weeks gestation. Following exclusion for death, with no retinal exam or incomplete data, 2791 (61%) were included in the study. Overall, severe ROP occurred in 260 (9.3%), but only 11/1601 ≥ 29 weeks (0.7%). All infants with severe ROP ≥ 29 weeks had at least 2 identified ROP risk factors. Implementation of this risk based screening strategy to the IHC population over the timeline of this study would have eliminated screening in 21% (343/1601) of the screened population. Conclusions. Limiting ROP screening for infants ≥ 29 and ≤ 32 weeks to only those with clinical risk factors could significantly reduce screening exams while identifying all infants with severe ROP.

Applying the resources and supports in self-management framework to examine ophthalmologist-patient communication and glaucoma medication adherence.

Little is known about how ophthalmologist-patient communication over time is associated with glaucoma patient long-term adherence. The purpose of our study was to examine the association between provider use of components of the resources and supports in self-management model when communicating with patients and adherence to glaucoma medications measured electronically over an 8-month period. In this longitudinal prospective cohort study, the main variables studied were ophthalmologist communication-individualized assessment, collaborative goal setting and skills enhancement. Patients with glaucoma who were newly prescribed or on glaucoma medications were recruited from six ophthalmology clinics. Patients' baseline and next follow-up visits were videotape-recorded. Patients were interviewed after their visits. Patients used medication event monitoring systems (MEMS) for 8 months after enrollment into the study, and adherence was measured electronically using MEMS for 240 days after their visits. Two hundred and seventy-nine patients participated. Patient race and regimen complexity were negatively associated with glaucoma medication adherence over an 8-month period. Provider communication behaviors, including providing education and positive reinforcement, can improve patient adherence to glaucoma medications over an 8-month period.

Disruption of the association of integrin-associated protein (IAP) with tyrosine phosphatase non-receptor type substrate-1 (SHPS)-1 inhibits pathophysiological changes in retinal endothelial function in a rat model of diabetes.

AIMS/HYPOTHESIS: We have previously shown that the association of integrin-associated protein (IAP) with tyrosine phosphatase non-receptor type substrate-1 (SHPS-1) regulates the response of cells, including osteoclasts, osteoblasts, smooth muscle and retinal endothelial cells, to IGF-I. Here we sought to: (1) determine whether the regulation of IGF-I responsiveness by the association of IAP with SHPS-1 is a generalised response of endothelial cells; (2) identify the mechanism by which this association contributes to changes in endothelial cell responses to IGF-I; and (3) determine whether inhibition of this association alters pathophysiological changes occurring in vivo. METHODS: Endothelial cells were maintained in 5 mmol/l glucose and at hyperglycaemic levels, and exposed to an anti-IAP antibody that disrupts the association between IAP and SHPS-1. A rodent model of diabetes with endothelial cell dysfunction was used to investigate the role of the association of IAP with SHPS-1 in endothelial cell function in vivo. RESULTS: Endothelial cells maintained in 5 mmol/l glucose showed constitutive cleavage of the extracellular domain of IAP (which contains the SHPS-1 binding site), with no association between IAP and SHPS-1 being detected. In contrast, hyperglycaemia inhibited IAP cleavage, allowing IAP to associate with SHPS-1 and IGF-I to stimulate SHPS-1 tyrosine phosphorylation. Exposure to the anti-IAP antibody inhibited IGF-I-stimulated tube formation and increased permeability. In the rodent model, basal IAP-SHPS-1 association was not detected in retinal extracts from normal rats, but was fully restored in rats with diabetes. The anti-IAP antibody inhibited the association of IAP with SHPS-1, and reduced retinal vascular permeability and leucocyte adherence to levels similar to those in non-diabetic rats. The antibody also significantly inhibited the aberrant neovascularisation induced by hypoxia. CONCLUSIONS/INTERPRETATION: Our results demonstrate that the increased association of IAP with SHPS-1 contributes to the pathophysiological changes in the endothelium that are induced by hyperglycaemia and hypoxia.

Predictive value of pre-plus disease in retinopathy of prematurity.

OBJECTIVES: To investigate prospectively whether the presence of pre-plus disease predicts progression to severe retinopathy of prematurity (ROP) requiring laser treatment. METHODS: Posterior retinal video recordings were obtained during 710 indirect ophthalmoscopy examinations of 214 premature infants over a period of 5 years. Two masked experts reviewed short video recordings and determined whether there was plus disease, pre-plus disease, or neither. The primary analysis included results of one examination of the right eye at 33 to 34 weeks' postmenstrual age. The primary outcome was a comparison of the proportion of eyes subsequently requiring laser treatment between the group graded as having pre-plus disease vs the group graded as having neither plus disease nor pre-plus disease. RESULTS: Of 10 eyes with pre-plus disease at 33 to 34 weeks' postmenstrual age, 7 (70%) subsequently required laser treatment; of 154 eyes without pre-plus disease or plus disease at 33 to 34 weeks' postmenstrual age, 14 (9%) subsequently required laser treatment (risk ratio, 7.7; 95% confidence interval, 4.1-14.8; P < .001). The mean time between the examination diagnosing pre-plus disease and laser treatment was 1.6 weeks (range, 1.0-2.4 weeks). When adjusting for birth weight, gestational age, ROP location (zone), and ROP severity (stage), the presence of pre-plus disease at 33 to 34 weeks' postmenstrual age independently predicted the need for laser treatment (adjusted odds ratio, 7.6; 95% confidence interval, 1.4-42.3; P = .02). CONCLUSIONS: Pre-plus disease observed early during the course of ROP is strongly associated with the development of severe ROP requiring laser treatment. The diagnosis of pre-plus disease has prognostic value beyond that already provided by birth weight, gestational age, ROP zone, and ROP stage. Eyes with pre-plus disease should be closely observed to allow optimal timing of intervention.

Development of an instrument to measure glaucoma medication self-efficacy and outcome expectations.

PURPOSE: The purpose of this study was to develop and evaluate the psychometric properties of (a) a glaucoma medication self-efficacy scale and (b) a glaucoma outcome expectations scale. PATIENTS AND METHODS: Two instruments were developed: a glaucoma medication self-efficacy scale and a glaucoma outcome expectations scale. Packets containing (a) the instruments and patient demographic questions and (b) a letter explaining the study were distributed to 225 glaucoma patients from three ophthalmology practices between August and December 2007. The instrument was completed by 191 patients for a response rate of 85%. Principal components factor analysis with a varimax rotation and Cronbach's alpha reliability were used to analyse the data. To assess discriminant validity, we administered the scales and two self-reported measures of adherence in a separate sample of 43 glaucoma patients who were currently using at least one glaucoma medication. RESULTS: Our results yielded a 21-item self-efficacy in overcoming barriers that might interfere with the use of glaucoma medications scale, a 14-item self-efficacy in carrying out specific tasks required to use eye drops correctly scale, and a four-item glaucoma outcome expectations scale. Results of the Cronbach's alpha reliability indicated that the scales are internally consistent. The self-efficacy scales were both significantly associated with two patient self-reported measures of glaucoma medication adherence, which show discriminant validity. CONCLUSIONS: Eye care providers and researchers can use these scales to identify patients with low self-efficacy in using their glaucoma medications and patients who do not believe that following their eye care providers' advice can help their vision.

Vascular endothelial growth factor in eye disease.

Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the US, for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

Serum markers of oxidative stress and severity of diabetic retinopathy.

OBJECTIVE: To compare serum markers of oxidative stress with diabetic retinopathy severity RESEARCH DESIGN AND METHODS: This cross-sectional study compared patients with types 1 and 2 diabetes with control subjects in western New York and Pennsylvania. Retinopathy severity was graded from funduscopic fields based on the Early Treatment of Diabetic Retinopathy Study. Serum samples were analyzed for thiobarbituric acid-reacting substances (TBARS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, creatinine, HbA1, and triglycerides. Appropriate analysis of covariance models were performed. RESULTS: TBARS (P = 0.019), triglyceride (P = 0.004), and glucose and HbA1 (both P<0.001) levels were elevated in diabetic patients compared with those in control subjects. SOD (P = 0.003) and GSH-Px (P = 0.046) levels were lower in diabetic patients than in control subjects. No correlation existed between SOD levels and either glucose or HbA1 levels. No significant associations existed between levels of TBARS, SOD, or GSH-Px and severity of diabetic retinopathy There was a significant association between poorer visual acuity and worse retinopathy (P = 0.009), which was only partly explained by macular edema. CONCLUSIONS: Increased levels of TBARS and decreased levels of SOD and GSH-Px were found in diabetic patients compared with those in control subjects, but no significant associations were found between the levels of these substances and severity of retinopathy When duration and type of diabetes and serum HbA1 levels were taken into account, only visual acuity remained associated with more severe retinopathy.

Infrared scanning laser tomography of macular cysts.

OBJECTIVE: To perform three-dimensional, noninvasive, quantitative analysis of cystoid macular edema and macular cysts using infrared scanning laser tomography and to correlate findings with visual acuity (VA) as a basis for interventional studies. DESIGN: Cross-sectional, nonrandomized study. PARTICIPANTS: Seventeen patients (29-86 years of age) with macular cysts associated with a broad spectrum of diseases. INTERVENTION: Confocal infrared imaging with scanning laser tomography with the TopSS (790 nm) (Laser Diagnostic Technologies, San Diego, CA) with digitized images was used to perform three-dimensional, quantitative analysis of cysts in the central 5 degrees of the macula. MAIN OUTCOME MEASURES: Measurements of macular cyst number, area, volume, depth, slope, height of the surrounding macular elevation, and correlation with VA. RESULTS: Scanning laser tomography detected macular cysts in all patients. The number per patient ranged from 1 through 15. Cysts were accompanied by surrounding macular elevation in 16 patients (mean macular height, 216 microm). The area covered by cysts in the central 5 degrees was 0.087 to 0.969 mm2, and volume was 0.007 to 0.549 mm3. Visual acuity was significantly poorer in patients with greater cyst area (P = 0.0007), cyst volume (P = 0.0009), macular thickening (P = 0.0002), and cyst depth (P = 0.0013). Cyst number, average slope, and maximum slope, however, did not correlate significantly with VA. Grouping of macular cysts according to macular height and average cyst depth revealed that cysts in a more thickened retina were significantly deeper, had steeper slopes, and corresponded to worse VA. Macular height and average cyst depth were highly associated with each other, suggesting that in eyes with surrounding macular edema, cysts were deeper and may reflect more widespread tissue destruction. Individual confocal tomographic images provided additional information. Neither ophthalmoscopy nor fluorescein angiography delineated features such as retinal folds that suggested vitreous traction or changes in deeper layers that suggested occult choroidal new vessels. CONCLUSIONS: Infrared scanning laser tomography is a rapid and noninvasive imaging method that provides quantitative analysis of macular cysts in addition to qualitative information not seen clinically. Because poor VA is related to severe involvement of the central retina, scanning laser tomography could provide an objective outcome measure for interventional studies.

Infrared imaging of cystoid macular edema.

BACKGROUND: Cystoid macular edema (CME), a cause of central visual loss, is described in various pathologies. Typically, the fluorescein angiogram confirms the diagnosis and provides qualitative information as to the extent of leakage. This study was performed to investigate the features of cysts and quantify the extent of CME using non-invasive infrared imaging. METHODS: Eighteen eyes of 16 successive patients with CME in association with a broad spectrum of diseases were included in the study. The diagnosis of CME was established clinically and confirmed by fluorescein angiography. Digital infrared imaging was performed with a research scanning laser ophthalmoscope with different apertures, providing direct confocal and indirect imaging modes, to discriminate superficial features from deeper ones and to emphasize sources of multiple laterally scattered light. RESULTS: CME was easily detected with infrared imaging in all eyes. Confocal mode visualized the cysts themselves, while indirect mode emphasized borders. Large central cysts were detected as distinct, non-confluent structures. In addition, folds detected with infrared imaging in the macula in 12 of the 18 eyes were not always observed clinically. CONCLUSION: Infrared imaging provides a quick and safe diagnostic tool for patients with CME. The cystoid structures are readily localized and quantified, useful for monitoring CME. Despite differences in the pathophysiology, cysts did not differ qualitatively in a variety of diseases with infrared imaging.

Release of bFGF, an endothelial cell survival factor, by osmotic shock.

PURPOSE: To test the effects of osmotic change on basic fibroblast growth factor (bFGF) release from cultured endothelial cells (ECs). METHODS: Bovine aortic and bovine retinal ECs were exposed to hypoosmotic shock for 2 minutes, were allowed to recover for 15 minutes, and had bFGF release assayed. The role of bFGF in cell recovery was assessed by including neutralizing antibody against bFGF or the addition of exogenous bFGF. Cell number and viability were determined under varying conditions. Apoptosis was assessed by immunoperoxidase detection of digoxigenin-labeled DNA. RESULTS: After shock and recovery, both ECs released significantly greater amounts of bFGF than untreated control. bFGF release after shock for 2 minutes was lower than release after shock and recovery. Bovine retinal endothelial (BRE) cell number was reduced at 48 hours after shock, recovery, and removal of released bFGF compared with cells left in the presence of released bFGF. Cell number was significantly lower when BRE cells were shocked and recovered in the presence of a neutralizing anti-bFGF antibody (P<0.05). Exogenous bFGF reversed this effect. Apoptosis was significantly increased in BRE cells shocked and recovered or in the presence of bFGF antibody (P<0.001). CONCLUSIONS: bFGF is released by cultured ECs in response to osmotically induced cell injury. These results support the concept of bFGF as a "wound" hormone and survival factor for ECs. In further compromised tissue, release of bFGF in this manner may play a role in the pathogenesis of disease.

Spatial extent of pigment epithelial detachments in age-related macular degeneration.

OBJECTIVE: To quantify the spatial extent of pigment epithelial detachment (PED) associated with age-related macular degeneration (AMD) using a rapid, noninvasive method. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: The authors tested 32 eyes of 21 patients (13 women and 8 men) with AMD 56 to 91 years of age (mean = 72.8 years). The authors retested seven eyes of six patients. INTERVENTION: Three-dimensional imaging and quantification of PED were performed in each subject using confocal infrared imaging (790 nm) with a Topographic Scanning System (TopSS). The data consisted of a series of 32 images within a 3-mm-depth range requiring 0.9 second. Three-dimensional calculations were made from the series. MAIN OUTCOME MEASURE: Height, diameter, area, volume, and slope of each PED were obtained with two calculation methods. The Ellipse Method used a graphics tool to draw elliptical borders circumscribing the region of interest in the image. The software automatically calculated the values for all parameters for the region inside the ellipse, with the retinal reference plane adjusted to match the height of the surrounding retina. The User-Defined Region Method differed in that the region of interest was drawn manually. RESULTS: PEDs were easily detected in all patients using the TopSS. Maximum height of all PEDs above the reference plane ranged from 0.204 to 1.818 mm (mean = 0.57 mm). The diameter was 0.501 to 5.151 mm (mean = 2.711 mm), area was 0.179 to 20.402 mm2 (mean = 6.585 mm2), and volume was 0.012 to 13.981 mm3 (mean = 2.173 mm3). Intraobserver variability was low, with correlations between first and second measurements for the first visit ranging from r = 0.906 to 0.997 for slope and diameter, respectively. CONCLUSIONS: Three-dimensional analysis with the TopSS provides objective outcome measures not obtainable with typical clinical methods such as fundus photography and angiography. Height and volume are crucial in determining whether neovascularization is worsening or persistent after photocoagulation. More longitudinal data are needed to determine whether tomographic data reduce the need for angiography. Unique to scanning laser tomography, exudative features were imaged at different depths.

Cyanoacrylate glue in the repair of retinal detachment associated with posterior retinal breaks in infants and children.

PURPOSE: To share the authors' experience with cyanoacrylate glue in posterior retinal breaks associated with retinal detachments in infants and children. METHODS: A retrospective study was performed of four consecutive pediatric patients who underwent vitreoretinal surgery for retinal detachment associated with posterior retinal breaks, for which cyanoacrylate glue was used. RESULTS: In three of the four patients, successful retinal reattachment with visual function was achieved by vitreoretinal surgery and cyanoacrylate placed on the apposed edges of posterior retinal breaks or used to plug a break (postoperative follow-up was 1.5-2 years). In two successful cases, the glue was applied onto the break while the retina was detached, which resulted in closure of the retinal breaks and reattachment of the retina in both cases. CONCLUSIONS: Cyanoacrylate creates a permanent closure of retinal breaks and may be useful in select cases of infant retinal detachment with posterior retinal breaks in which current available treatment failed or would fail.

Quantitative analysis of macular holes with scanning laser tomography.

OBJECTIVE: The purpose of the study is to establish objective, quantitative, and reproducible three-dimensional analysis for macular holes with scanning laser tomography and to correlate measurements with visual acuity. DESIGN: The authors performed a cross-sectional, nonrandomized study. PARTICIPANTS: The authors examined 28 full-thickness macular holes of 23 patients aged 61 to 84 years. INTERVENTION: Confocal infrared imaging with scanning laser tomography using the TopSS (790 nm, 10 degrees field) three-dimensional measurements and macular hole analysis were performed. MAIN OUTCOME MEASURES: Area, depth, and volume parameters for both macular holes and rims were obtained in two ways: (1) reference plane for analysis equal to height of the retina (offset surface distance [OSD] 0) or (2) equal to height of the surrounding edematous rim of the hole (OSD user). Correlation of measurements with visual acuity and groups of macular holes was performed. Reproducibility from three image series per subject and intraobserver variability from ten measurements in four subjects were computed. RESULTS: Scanning laser tomography could detect macular hole and rim features in all subjects. Infrared images provided clinically useful information that may help explain macular hole pathophysiology. Based on quantitative, three-dimensional measurements, holes were assigned to four groups: large, small, shallow, and average. Groups varied significantly (P < 0.05) for the majority of measurements. Visual acuity correlated significantly (P < 0.05) with macular hole volume, depth, slope, and rim height with OSD user only, but not with hole area. Holes computed with OSD user were deeper and of greater volume. Reproducibility was excellent for hole area, slope, and rim area; good for hole volume and depth; variable for rim volume; and improved with OSD user. Intraobserver variability was low in each group. CONCLUSIONS: Scanning laser tomography is a reproducible three-dimensional imaging technique providing objective and quantitative clinical information in assessing, grouping, and managing macular holes. By setting the OSD to rim height, additional information of rim height and hole volume was provided and correlated with visual acuity. In addition, more reliable differences among macular hole groups were found. Axial measurements such as macular hole depth, volume, and rim height may be more important for visual acuity than hole area indicating their possible predictive value for outcome measures.

Deep retinal vascular anomalous complexes in advanced age-related macular degeneration.

PURPOSE: The authors describe the clinical characteristics of a group of patients with age-related macular degeneration (AMD), deep retinal vascular anomalous complexes (RVACs), advanced Bruch membrane changes, and severe visual loss. Based on clinical evaluation and imaging studies, the authors hypothesize the cause of such retinal vascular formations. PATIENTS AND METHODS: The authors quantified an initial case series of 6 patients and expanded it to 11 patients (14 eyes) with AMD and RVACs diagnosed by fluorescein angiography or slit-lamp examination. Associated pigment epithelial detachments (PEDs) of 13 eyes are described. In addition to the clinical and fluorescein angiography descriptions, infrared imaging and indocyanine green angiography were used to characterize more recently described RVACs and fellow eyes. RESULTS: Each study eye had a clearly defined anastomosis connecting the retinal circulation to a vascular complex in the deep retina. The RVACs associated with PEDs assumed a more central location than did typical choroidal neovascularization associated with PEDs. In seven eyes with RVACs, there were clinically recognizable retinovascular findings: intraretinal hemorrhages, telangiectasia, or microaneurysms. Legal blindness occurred in 9 of 11 patients. CONCLUSION: These results indicate that retinovascular changes can be associated with nondisciform AMD. The authors speculate that neurodegenerative changes and hypoxia may lead to such changes, the RVAC being a more advanced finding. Closure of an RVAC with photocoagulation is difficult, perhaps because of its higher blood flow. The visual outcome is poor, not only because of the advanced state of the underlying AMD, but also because of the exudative nature of the RVAC.

Characteristics of exudative age-related macular degeneration determined in vivo with confocal and indirect infrared imaging.

PURPOSE: To evaluate the current and future interventions in age-related macular degeneration (AMD), it is essential to delineate the early clinical features associated with later visual loss. The authors describe the retinal pigment epithelium (RPE)/Bruch membrane region in ten patients with advance exudative AMD using current angiographic techniques and a noninvasive method: infrared (IR) imaging with the scanning laser ophthalmoscope. METHODS: Ten patients with exudative AMD, evidence by choroidal neovascularization (CNV), fibrovascular scar formation, pigment epithelial detachment, or serous subretinal fluid,were examined using IR imaging, fluorescein angiography, indocyanine green angiography, and stereoscopic viewing of fundus slides. The authors determined the number and size of drusen and subretinal deposits and the topographic character of the RPE/Bruch membrane area and of CNV. RESULTS: In all patients, IR imaging yielded the greatest number of drusen and subretinal deposits. Sheets of subretinal material, but few lesions consistent with soft drusen, were seen. Infrared imaging provided topographic information of evolving CNV. Choroidal neovascularization appeared as a complex with a dark central core, an enveloping reflective structure which created a halo-like appearance in the plane of focus, and outer retinal/subretinal striae. CONCLUSIONS: Infrared imaging provides a noninvasive, in vivo method to image early changes in the RPE/Bruch membrane. It offers advantages over current imaging techniques by minimizing light scatter through cloudy media and enhancing the ability to image through small pupils, retinal hyperpigmentation, blood, heavy exudation, or subretinal fluid. It provides additional information regarding early CNV, and the character of drusen and subretinal deposits.

Difficulties in excluding the diagnosis of retinoblastoma in cases of advanced Coats' disease: a clinicopathologic report.

We highlight the difficulty in differentiating Coats' disease from retinoblastoma. Two patients with bullous exudative retinal detachment and abnormal vessels are discussed. Histologic evaluation of the 5-year-old patient revealed retinoblastoma. The 1-year-old patient had Coats' disease by histologic identification. With this in mind, we suggest enucleation of such eyes if diagnostic uncertainty exists, since failure to treat retinoblastoma is a more serious error than enucleation of an eye with minimal function.